1/8. Neutrophil and endothelial cell activation in the vasa vasorum in vasculo-Behcet disease.AIM: The aim of this study was to analyse the immunopathological mechanisms of vasculo-Behcet disease, which were also compared to cases of Takayasu's arteritis and inflammatory aneurysm to evaluate differences in inflammatory mechanisms. METHOD AND RESULTS: We reviewed six cases of vasculo-Behcet disease, four of Takayasu's arteritis and seven inflammatory aneurysms which underwent surgical repair. Immunohistochemical studies were performed on paraffin-embedded tissue using a labelled streptavidin-biotin method, as was in-situ hybridization for Epstein-Barr virus. Microscopically, neutrophils and lymphocytes accumulated around the vasa vasorum. neutrophils were prominent as compared to Takayasu's arteritis and inflammatory aneurysm. Elastic fibres were not severely destroyed. endothelial cells (ECs) of most vasa vasorum expressed HLA-DR. The number of vasa vasorum around which inflammatory infiltrating cells were observed in vasculo-Behcet disease was significantly greater than in inflammatory aneurysms and Takayasu's arteritis (P < 0.001). The cytokines IL-1alpha, TNF-beta and IFN-gamma were expressed in neutrophils and lymphocytes which were distributed around vasa vasorum, as well as neutrophils adherent to HLA-DR positive ECs. CONCLUSION: Our results suggest that vasculo-Behcet disease should be classified as a neutrophilic vasculitis targeting the vasa vasorum. aneurysm formation may be related to degeneration of arterial wall caused by inflammation of the vasa vasorum.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/8. Benign lymphocytic angiitis and granulomatosis: a T-cell lymphoma?Benign lymphocytic angiitis and granulomatosis is a T-cell lymphoproliferative disorder confined to the lung and corresponding to a low-grade angiocentric immunoproliferative lesion. Controversy remains as to whether these lesions are lymphomas. We report such a case in an 8-year-old patient with Burkitt's lymphoma in remission who presented with persistent bronchopneumopathy and bilateral pulmonary infiltrates on tomodensitometry. Surgical resection revealed the histologic changes of benign lymphocytic angiitis and granulomatosis. immunohistochemistry showed no aberrant pan T-cell marker loss. Genetic analysis of frozen tissue by Southern blot dna hybridization with probes to T-cell receptor beta- and gamma-chain genes and to the immunoglobulin heavy chain joining region gene (JH) identified no clonal rearrangement. Search for Epstein-Barr virus-dna sequences by in situ hybridization and Southern blot analysis provided negative results. Our data imply that lowgrade angiocentric immunoproliferative lesions are not exclusively lymphomas but might represent a borderline lymphoproliferative disease (seen in the course of many diseases), perhaps corresponding to host immune response.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
3/8. Systemic lupus erythematosus and concurrent cytomegalovirus vasculitis: diagnosis by antemortem skin biopsy.A 45-year-old woman with a 4-year history of systemic lupus erythematosus (SLE) developed fever, decreased visual acuity and skin ulceration. A biopsy of a cutaneous ulcer demonstrated small vessel vasculitis with characteristic cytomegalovirus (CMV) inclusions in the vascular endothelium. The presence of CMV was confirmed by dna hybridization immuno-histochemistry. retinal artery vasculitis, previously associated with flares of her SLE, was also noted on ophthalmologic examination. Our case demonstrates that CMV infection can mimic the cutaneous manifestations of collagen vascular disease and that early identification can be made by biopsy of suspicious skin lesions.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/8. Necrotizing lymphoid vasculitis in X-linked lymphoproliferative syndrome.An 8-year-old maternally related relative of three boys who had developed agammaglobulinemia associated with Epstein-Barr virus (EBV)-induced infectious mononucleosis was studied for X-linked lymphoproliferative syndrome (XLP) in 1979. At that time, he demonstrated no striking immunologic aberrations and was seronegative for EBV. Subsequently, immunologic abnormalities including failure to switch from IgM to IgG antibody synthesis after secondary immunization with bacteriophage phi X174 were detected. In 1983, he experienced episodic intracerebral hemorrhages, with the second being fatal. At autopsy, necrotizing vasculitis and aneurysms involving arteries of the central nervous system were observed. Studies of blood obtained immediately before and after death failed to show antibodies to EBV. However, EBV genome was demonstrated in tissues obtained at autopsy by dna hybridization studies. Fatal lymphoid vasculitis in this patient is unique among boys with XLP in the registry. These findings probably extend the phenotypic expressions of XLP.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/8. A rare mediastinal tumour presenting with systemic effects due to IL-6 and tumour necrosis factor (TNF) production.patients presenting with prolonged systemic illnesses with no specific clinical or serological defining features may be diagnosed as having atypical systemic vasculitides, but often turn out to have occult malignancies. cytokines have been implicated in causing many of the systemic effects in such cases. In this study we describe a patient presenting after 2 years of a severe systemic illness with a marked acute phase response, due to an occult mediastinal angiomatoid malignant fibrous histiocytoma. Tumour resection was curative. We evaluated in detail the local and systemic production of cytokines induced by this tumour. Blood samples were taken pre- and post-operatively for cytokine studies. in vitro production of IL-2, IL-2R, IL-1 beta, IL-6 and TNF-alpha by cultured monocytes from the patient, as well as plasma cytokine levels, were measured by ELISA. Tumour cytokine production was also evaluated immunocytochemically, and by in situ hybridization with specific cDNA probes. plasma IL-2R and IL-6, and IL-6 and TNF-alpha production by peripheral blood monocytes were markedly elevated before tumour resection, normalizing post-operatively. Most tumour cells and infiltrating lymphocytes stained with antibodies to IL-6, IL-6R and TNF-alpha, and expressed HLA class II. IL-6 and TNF-alpha mRNA production in the tumour was confirmed by in situ hybridization studies. We have described the first case of an occult angiomatoid malignant fibrous histiocytoma in the mediastinum. Studies of cytokine expression suggested that chronic TNF, IL-6, and IL-2 production by leucocytes and tumour cells in this patient was responsible for the severe systemic illness with which she presented.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
6/8. Varicella-zoster virus infection of the central nervous system in the acquired immune deficiency syndrome.Productive varicella-zoster virus (VZV) infection of the central nervous system (CNS) was demonstrated in 11 acquired immune deficiency syndrome (AIDS) patients using immunocytochemistry and in situ hybridization. A characteristic zoster skin eruption was seen in only four cases. From our own series and 11 other cases in the literature, we identified five clinico-pathological patterns of VZV infection of the CNS in AIDS patients which could occur simultaneously. (i) Multifocal encephalitis predominantly involving the white matter, likely to be due to haematogenous spread of the infection was found in four cases. (ii) Ventriculitis was found in three cases. In two cases there was complete acute or chronic necrosis of the ventricular wall with marked vasculitis; in the third, the ependymal lining appeared irregular with foci of VZV-infected ependymal cells, some of which protruded into the ventricular lumen. (iii) Acute haemorrhagic meningo-myeloradiculitis with necrotizing vasculitis was observed in two cases. In one, this was associated with ventriculitis and was possibly due to shedding of infected ependymal cells into the ventricular lumen and secondary seeding of the CSF. (iv) Focal necrotizing myelitis was seen in one case. It followed cutaneous herpes zoster and was considered to result from neural spread from the diseased dorsal root ganglion similar to cases previously described of encephalitis limited to the visual system following VZV ophthalmicus, or bulbar encephalitis following a trigeminal zoster. (v) Vasculopathy involving leptomeningeal arteries and causing cerebral infarcts was seen in four cases, it was associated with meningitis in most cases. These findings are in keeping with the observation in non-AIDS patients that VZV spread to the CNS may follow different routes. Our study tends to show that VZV infection of the CNS occurs more frequently in AIDS than previously suspected and suggests that it must be considered as a diagnosis in cases of encephalitis, ventriculitis, focal myelitis, acute myeloradiculitis and cerebral infarcts in these patients.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/8. Clonal CD5-positive B lymphocytes in myelodysplastic syndrome with systemic vasculitis and trisomy 8.Bone marrow and peripheral blood from a myelodysplastic syndrome (MDS) patient with trisomy 8 and associated systemic vasculitis was investigated for clonal lymphoid lineage involvement using simultaneous metaphase and interphase fluorescence in situ hybridization (FISH) and immunocytochemistry with antibodies against CD13 (granulocytic), glycophorin A (GPA, erythroid), and the lymphocytic antigens CD3. CD5, CD20, and CD22. trisomy 8 was detected in 55% of CD13 , 40% of GPA , 6% of CD5 , and 5% of CD20/22 , but not in CD3 cells. In a complementary experiment using interphase FISH on bone marrow cells sorted by flow cytometry, 13% of CD5/CD19 double-positive cells (76% purity) were found to be trisomic. The results indicate the existence of a small CD5-positive B-lymphoid clone as part of the MDS process in this patient. Since CD5/19-positive cells have been proposed to be autoantibody producing, this finding might be a clue to the pathogenesis underlying the propensity for MDS patients to develop immune-mediated complications.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/8. Profound cerebrospinal fluid pleocytosis and Froin's syndrome secondary to widespread necrotizing vasculitis in an hiv-positive patient with varicella zoster virus encephalomyelitis.Demonstration of the direct involvement of cranial blood vessels by varicella zoster virus (VZV) is facilitated by immunohistochemistry (IHC), in situ hybridization (ISH) and polymerase chain reaction (PCR) techniques. The extent to which an inflammatory vasculitis serves as the pathogenic mechanism for VZV encephalomyelitis (VZVE) is still, however, debated. Most VZVE patients are immunocompromised and show little inflammation, either pre-mortem in cerebrospinal fluid (CSF) or at autopsy. We describe an hiv-positive patient with a moderately depressed CD4 count (304) who presented with massively elevated CSF protein (1800 mg/dl), bloody CSF and pleocytosis (1300 white blood cells (WBC)/mm3). His CSF was positive for VZV dna by PCR. He was treated with acyclovir and foscarnet, but died. At autopsy, an unusually widespread, inflammatory, transmural vasculitis caused by VZV affected meningeal vessels at virtually all brain stem and spinal cord levels, causing multiple subpial hemorrhages and necrosis. Virus dna in multiple areas of brain, brainstem and spinal cord was readily revealed by PCR, but not by the presence of viral inclusions, IHC or ISH. This case, with a clinically confusing presentation for VZVE, illustrates the extensive, albeit infrequent, degree of necrotizing vasculitis and CSF abnormalities that VZV is capable of producing. Antiviral therapy may have inhibited VZV genome replication and subsequent antigen production, resulting in negative ISH and IHC studies, but generated increased VZV genomic fragments that were detectable by the more sensitive PCR technique.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |